Cesium fluoride → HCID 117843278, compound

Participants

Reaction Conditions

Reaction Steps

Intermediate 2.06 (29 mg, 0.098 mmol), Pd-PEPPSI-IPent precatalyst (4 mg, 0.005 mmol), cesium fluoride (32 mg, 0.21 mmol) and powdered 4 Å molecular sieves (25 mg) were taken up in dioxane (1 mL) under Ar. 1-methyl-5-(tributylstannyl)-1H-thieno[3,2-c]pyrazole (46 μL, 0.13 mmol) was added and the resulting mixture was heated to 65-70° C. After 2 h, the reaction temperature was increased to 80° C. After 18 additional hours, additional Pd-PEPPSI-IPent precatalyst (3 mg, 0.004 mmol), CsF (35 mg, 0.23 mmol) and stannane (23 μL, 0.065 mmol) were added and the reaction was heated to 80° C. After an additional 3 h, additional Pd-PEPPSI-IPent precatalyst (5 mg, 0.006 mmol) was added and the reaction was stirred at 80° C. overnight. After 16 additional hours, the reaction mixture was partitioned between EtOAc and water. The phases were separated, and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated to afford a crude residue that was purified by silica gel chromatography (MeOH in DCM) to provide (R)-4-((R)-1-(3-methyl-6-(1-methyl-1H-thieno[3,2-c]pyrazol-5-yl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.23. LCMS-ESI+ (m/z): [M+H]+ calcd for C19H21N6O2S: 397.1; found: 397.2. 1H NMR (400 MHz, Chloroform-d) δ 7.86 (s, 1H), 7.70 (s, 1H), 7.63 (d, J=0.7 Hz, 1H), 7.35 (d, J=0.7 Hz, 1H), 5.74-5.65 (m, 1H), 5.53 (s, 1H), 4.06 (s, 3H), 4.02 (d, J=0.4 Hz, 3H), 3.66-3.58 (m, 1H), 3.45-3.39 (m, 1H), 3.02-2.88 (m, 1H), 2.63-2.48 (m, 2H), 1.52 (d, J=6.3 Hz, 3H).

Provenance & Evidence